This report describes developmental and epileptic encephalopathy 4, a subtype of evelopmental and epileptic encephalopathy. The human gene implicated is STXBP1, which encodes a syntaxin-binding protein. There is one high-scoring fly ortholog, Dmel\Rop, for which multiple genetic reagents, including amorphic alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
Wild-type Hsap\STXBP1 has been introduced into flies, but has not been used to model disease.
Pan-neuronal or dopaminergic neuron-specific RNAi knockdown of Dmel\Rop is lethal at larval or pupal stages; homozygous amorphic Dmel\Rop alleles also result in lethality. Flies heterozygous for amorphic Dmel\Rop alleles survive to adulthood and exhibit a 20% decrease of Rop protein in heads, similar to decreases of STXBP1 protein in haploinsufficient patient iPSC-derived neurons, and in the brains of heterozygous mice. Flies haploinsufficient for Dmel\Rop exhibit exacerbation of the phenotypes induced by expression of Hsap\SNCA, including enhancement of rough eye and locomotor phenotypes.
[updated Dec. 2024 by FlyBase; FBrf0222196]
[DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 4; DEE4](https://omim.org/entry/612164)
[SYNTAXIN-BINDING PROTEIN 1; STXBP1](https://omim.org/entry/602926)
Developmental and epileptic encephalopathy-4 (DEE4) is a neurologic disorder characterized by the onset of tonic seizures in early infancy (usually in first months of life). In most cases, seizures increase in frequency and become refractory. Affected individuals have profoundly impaired psychomotor development with poor head control, limited or no ability to walk, spastic quadriplegia, and poor or absent speech. Brain imaging may show cortical atrophy and hypomyelination. EEG studies in the more severe cases show a burst-suppression pattern, consistent with a clinical diagnosis of Ohtahara syndrome, and/or hypsarrhythmia, consistent with a clinical diagnosis of West syndrome. Less severely affected individuals have later onset of seizures (summary by Saitsu et al., 2008, pubmed:18469812 ; Hamdan et al., 2009, pubmed:19557857). [from MIM:612164; 2024.12.03]
Developmental and epileptic encephalopathy-4 (DEE4) is caused by heterozygous mutation in the STXBP1 gene on chromosome 9q34. One family has been reported with a homozygous mutation in the STXBP1 gene. [from MIM:612164; 2024.12.03]
STXBP1 encodes a syntaxin-binding protein. The encoded protein appears to play a role in release of neurotransmitters via regulation of syntaxin, a transmembrane attachment protein receptor. [provided by RefSeq, Feb 2010]
Many to one (many human to 1 Drosophila); STXBP1 has one low-scoring Drosophila ortholog, Rop.
High-scoring ortholog of human STXBP1, moderate scoring ortholog of STXBP2 and STXBP3 (1 Drosophila to many human).
